Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10

Seung-Ha Yang,Min-Jung Park,Il-Hee Yoon,Su-Young Kim,So-Hee Hong,Jin-Young Shin,Hye-Young Nam,김용희,Bongi Kim,박정규 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naïve or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naïve and pre-activated T cells in which IL-10 and IDO play important roles.

감껍질 열수 및 초임계 유체 추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),신재영(Jae Young Shin),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.3

본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.

Ownership Structure of Northeast Asian Countries

Seung Rok Park,Peter Drysdale,Shin Il Kang,In kie Hong 한국경제연구원 2004 한국경제연구원 연구보고서 Vol.2004-02 No.-

1 In the first paper “Determinants of Corporate Ownership Structure and their effects on Corporate Governance in South Korea” by Shin-Il Kang, Korea’s unique characteristics, specifically the ownership structure and corporate governance are examined. The author takes a broad perspective by incorporating corporate culture, business leadership, and ownership structure in Korean corporation. Furthermore, he discusses the substitutability of Korean specific features given the rapidly changing economic environment. Under the Korea’s Chaebol structure, controlling shareholders, who are the real owner of firms, have exercised ownership rights while having a large proportion of shares aided by cross shareholdings. This has been possible through the pyramid ownership control structure as well as cross-shareholding among subsidiaries. Market circumstances related to management costs are not favorable to the firm with a dispersed ownership structure. In Korea, that’s the reason why ownership is concentrated. Given such a structure, the owners minimize costs related to management’s risks. Furthermore it proposes that leadership(firm culture) and ownership are substitutes. Concentrated ownership is needed when the leadership is not mature like Korean Chaebol. 2 The second paper “Issues in Japanese Corporate Governance” by Peter Drysdale examines some of the major issues of Japanese corporate governance today. The role of that main bank in corporate governance and inter corporate shareholding has been well documented. Although Japanese banks have rigorously monitored firms and have had an enormous influence on firms’ decisions and strategies through the owning of shares, firm performance under such a main bank system has not always been positive. Opposing views and their rationale regarding the pessimism behind the performance of firms in the main bank system are also explained in this paper. 3 The paper “Corporate Governance in China” by In Kie Hong discusses the current status and the restructuring efforts of China’s corporate governance. In China, state shareholders possess strong control rights over listed companies allowing them to exercise control even beyond their proportion of shareholding. Various governmental organizations(under the Communist Party) acting as representatives of the state as shareholders have influenced firms enormously, particularly regarding matters of organizing the board of directors as well as electing management. However since they have little incentives to manage state(national) assets and have insufficient capacity to monitor a large number of firms of which they are in charge, the principal-agent problem tends to prevail, which adds to the difficulties in preserving the value of state assets as well. 4 The last paper “Ownership Concentration and Corporate Performances in the Northeast Asian Countries” by Seung-Rok Park compares the relationship between corporate governance structure and corporate performance in Korea, Japan, and China by empirically examining the accounting corporate performances and technical efficiency measures. In the case of Korea, ownership concentration was shown to have positively affected all corporate accounting performance variables such as profit margin, return on shareholders’ funds, return on total assets, and return on capital employed. Furthermore, it was also found that ownership concentration positively affected corporate performance by helping improve the technical efficiency of firms. Unlike Korea, in Japan, there was no sign of a positive effect of ownership concentration on the accounting corporate performance and technical efficiency. Moreover, in the case of China, ownership concentration positively affected profit margin and return on total assets, while no positive effects of ownership concentration were found on return on capital employed and return on shareholders’ funds. It is shown in this study that the difference in the rel

P179 : Activin suppresses LPS-induced Toll-like receptors, cytokines, and nitric oxide expression by inhibiting activation of NF-κB and MAPK pathways in normal human melanocytes

( Young Il Kim ),( Seung Won Park ),( Jeong Hwee Choi ),( Myong Il Bae ),( Min Kyung Shin ),( Mu Hyoung Lee ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-β (TGF-β) superfamily. Objectives: To know the mechanism how activin regulates transcription of lipopolysaccharide (LPS)-induced Toll-like receptors (TLRs), cytokines, and inducible nitric oxide synthase (iNOS) in human melanocytes, and the involvement of nuclear transcription factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Methods: Normal human melanocytes were pretreated with activin A before exposure to LPS. Total RNAs were purified and real-time PCR was performed. Also we conducted immunoblot analysis to know the expression levels of proteins. Results: LPS increased mRNA expressions of TLRs (1-10) and cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α), and enhanced mRNA and protein expression of iNOS. Activin inhibited LPS-induced mRNA expressions of TLRs and cytokines, and decreased mRNA and protein expression of LPS-induced iNOS. Also activin suppressed NF-κB p65 activation and blocked IκBα degradation in LPS-stimulated melanocytes, and reduced LPS-induced p38 MAPK and MEK/ERK activations. Conclusion: Activin inhibited expression of genes of TLRs, cytokines, and iNOS in LPS-activated normal human melanocytes. Moreover, anti-inflammatory effect of activin was mediated through suppressing activation of NF-κB and MAPKs signaling pathways in LPS-activated normal human melanocytes, resulting in reduced expression of TLRs, cytokines, and nitric oxide.

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

Comparison of inflammatory markers for the prediction of neointimal hyperplasia after drug-eluting stent implantation

Kang, Woong Chol,Il Moon, Chan,Lee, Kyounghoon,Han, Seung Hwan,Suh, Soon Yong,Moon, Jeonggeun,Shin, Mi Seung,Ahn, Taehoon,Shin, Eak Kyun Lippincott Williams Wilkins, Inc. 2011 Coronary artery disease Vol.22 No.8

BACKGROUND: We compared the relationship between inflammatory markers and neointimal hyperplasia (NIH) after drug-eluting stent (DES) implantation. METHODS: We implanted a single DES in 42 consecutive patients with stable angina. The plasma high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) levels were measured before, and 24 and 72 h after the procedure. Angiography and intravascular ultrasound were performed. RESULTS: No relationship was noted between the baseline hs-CRP level and NIH. A significant positive correlation was noted between NIH and the hs-CRP level obtained at 24 h (r=0.435, P=0.004), and 72 h (r=0.334, P=0.031) after the procedure. Interestingly, there was a positive correlation between the change (&Dgr;) in the hs-CRP level and NIH at 24 h (r=0.414, P=0.006). The fourth quartile of the hs-CRP at 24 h after percutaneous coronary intervention (PCI) had significantly larger volume of NIH than the first quartile (20.1±25.1 vs. 2.7±6.4 mm, P<0.05). Moreover, NIH in the fourth quartile (20.9±26.4 mm) was higher than the first quartile (3.3±8.6 mm) of the &Dgr; hs-CRP level at 24 h (P<0.05) after the procedure. Although the IL-6 level at the baseline and 72 h after the procedure were positively correlated with NIH (r=0.337, P=0.029 and r=0.435, P=0.004, respectively), the &Dgr; IL-6 level at any stage was not correlated with NIH. Neither the MMP-9 level nor the &Dgr; MMP-9 level at any stage was correlated with NIH. CONCLUSION: This prospective intravascular ultrasound study showed the inflammatory response after PCI, as measured by hs-CRP levels, but not the baseline hs-CRP level, predict NIH after DES implantation. Neither a change in the IL-6 nor MMP-9 levels at any stage after PCI reflected NIH.

관절1호방이 Collagen Ⅱ로 유발된 관절염 억제에 관한 연구

한규진 ( Kyu Jin Han ),진광선 ( Kwang Seon Jin ),신혜란 ( Hye Ran Shin ),윤일지 ( Il Ji Yoon ),최승훈 ( Seung Hoon Choi ),오민석 ( Min Seok Oh ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.4

Objectives : The aim of this study was to know the immunity responses of Gwanjulbang-1(Quanjiefang-1)(hereinafter referred to GJB-1) to on Rheumatoid Arthritis in Collagen-induced Arthritis(CIA) Mice Methods : For this purpose, experiments were performed to measure the cytotoxicity against mLFC, hFLSs and the production of proinflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ in hFLSs and the production of pro-inflammatory cytokines IL-4, IL-10 and the value of CD3+(T), CD19+(B), CD3+/CD69+, CD4, γδ T cells, CD4+/CD25+ Results : 1. The cytotoxicity against mLFC, hFLSs were not measured. 2. The production of pro-inflammatory cytokines IFN-γ were reduced in hFLSs. 3. The production of pro-inflammatory cytokines IL-4, IL-10 were increased. 4. Statistically significant value of CD3+(T), CD19+(B), CD3+/CD69+, CD4, γδ T cells, CD4+/CD25+ compared with control group, wild type, MTX. Conclusions : Comparison of the results for this study showed that GJB-1 had immunomodulatory effects of suppressing or enhancing. So we expect that GJB-1 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

Characterization of IL-3, IL-5, GM-CSF - induced Eosinophils from Human CD34+ Cord Blood Cells

( Kwang Shin Lee ),( Kang Mo Ahn ),( Seung Yeon Nam ),( Dae Yeul Son ),( Se Chang Han ),( Man Yong Han ),( Sang Il Lee ) 대한 소아알레르기 호흡기학회(구 대한소아알레르기 및 호흡기학회) 1999 소아알레르기 및 호흡기학회지 Vol.9 No.4

GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses

Kim, Il-Kyu,Koh, Choong-Hyun,Jeon, Insu,Shin, Kwang-Soo,Kang, Tae-Seung,Bae, Eun-Ah,Seo, Hyungseok,Ko, Hyun-Ja,Kim, Byung-Seok,Chung, Yeonseok,Kang, Chang-Yuil American Association for Cancer Research 2019 Cancer immunology research Vol.7 No.3

<P>Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions as an adjuvant for antitumor immunity through an unclear mechanism. By activating monocyte-derived dendritic cells, GM-CSF induces Th9 development and IL9 production, which facilitates antitumor cytotoxic T lymphocyte responses.</P><P>GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF–induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2–PGE<SUB>2</SUB> pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells <I>in vitro</I> and <I>in vivo</I>. GM-CSF–activated monocyte-derived dendritic cells converted tumor-specific nai¨ve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.</P>

Whole-Blood Gene-Expression Profiles of Cows Infected with Mycobacterium avium subsp. paratuberculosis Reveal Changes in Immune Response and Lipid Metabolism

( Min Kyoung Shin ),( Hong Tae Park ),( Seung Won Shin ),( Myung Hwan Jung ),( Young Bin Im ),( Hyun Eui Park ),( Yong Il Cho ),( Han Sang Yoo ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.2

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic debilitating disease affecting ruminants worldwide. In the present study, we aimed to determine the major gene networks and pathways underlying the immune response to MAP infection using whole-blood cells, as well as provide the potential transcriptional markers for identifying the status of MAP infection. We analyzed the transcriptional profiles of wholeblood cells of cattle identified and grouped according to the presence of MAP-specific antibodies and the MAP shed by them. The grouping was based on the results obtained by ELISA and PCR analyses as follows: i) Test1 group: MAP-negative results obtained by ELISA and positive results obtained by PCR; ii) Test2 group: MAP-positive results obtained by ELISA and negative results obtained by PCR; iii) Test3 group: MAP-positive results obtained by ELISA and positive results obtained by PCR; iv) uninfected control: MAP-negative results obtained both by ELISA and PCR analysis. The results showed down-regulated production and metabolism of reactive oxygen species in the Test1 group, activation of pathways related to the host-defense response against MAP (LXR/RXR activation and complement system) in the Test2 and Test3 groups, and anti-inflammatory response (activation of IL-10 signaling pathway) only in the Test3 group. Our data indicate a balanced response that serves the immune-limiting mechanism while the host-defense responses are progressing.